PROJECT SUMMARY The increasing trend in human exposure to engineered nanomaterials (ENMs) calls for interdisciplinary researches to assess the biological impacts from nanomaterials and discover the fundamental factors that contribute to such impacts. We hypothesize that, the surface and other physicochemical properties of engineered nanomaterials (ENMs) affect adsorption of biomolecules like proteins, and the corona formed by the adsorbed biomolecules subsequently mediate interaction with biological systems. To test this hypothesis, our integrated study carried out by a team of chemists, immunologists, and environmental engineers will look at the effects of these interactions on activation of inflammatory and immune responses in tissues, as well as the effect on the dynamic microbial community in the gut. Our focus will be mainly on the interactions between environmental ENMs and mucosal tissues such as the airways and gut, where individuals will first encounter the ENMs; consequently, cellular interactions will also focus on lung alveolar macrophages and epithelium, intestinal epithelium, and mucosal immune tissues. We will also study the effects of chronic exposure on tissues in vivo using an environmental chamber. Three specific aims are incorporated into our research program: (1) To generate and characterize the corona-bearing ENMs for in vitro and in vivo study and dissect the relationship between corona formation and ENM's physicochemical properties; (2) To acquire the in vitro and in vivo toxicity and immune response profiles induced by corona-carrying ENMs and determine the impact of sub-chronic and chronic exposure to inhaled ENMs on cell and tissue responses to antigen; and (3) To analyze impacts from the corona-carrying ENMs on gut microbiomes. Our work will identify the protein fingerprints of the coronas formed in the exposure-relevant biological fluids, discover the correlation between corona composition and a collection of ENM properties, and reveal the biological responses from cells, tissues, and mice to the corona-carrying ENMs. Together, we will provide an integrated and comprehensive view of the biological and health impacts of nanomaterials in our environment. The long term goal of our work is to deliver knowledge that could help to predict the biological impacts of ENMs by their physicochemical properties.